Venom-derived peptides targeting potassium channels: a strategy for precision immunomodulation in autoimmune diseases

Background and aim Autoimmune diseases (ADs) arise from the breakdown of immune tolerance, leading to autoreactive lymphocyte activation, chronic inflammation, and progressive tissue damage. Increasing evidence identifies potassium channels—particularly voltage-gated Kv1.3 and calcium-activated KCa3.1—as critical regulators of immune cell activation, calcium signaling, and cytokine production. Upregulation of Kv1.3 in effector memory T cells has been strongly associated with diseases such as systemic lupus erythematosus and multiple sclerosis. This review aims to evaluate the therapeutic potential of venom-derived peptides, especially scorpion toxins, as selective Kv1.3 blockers for precision immunomodulation in autoimmune disorders.Experimental approach A comprehensive analysis of preclinical and translational studies was conducted, focusing on the molecular mechanisms, pharmacological properties, and therapeutic efficacy of venom-derived Kv1.3-blocking peptides in established autoimmune disease models, including lupus and experimental autoimmune encephalomyelitis (EAE).Key findings Venom-derived peptides demonstrate high potency and remarkable selectivity for Kv1.3 channels, enabling targeted suppression of effector memory T cells while sparing other immune subsets. In lupus models, selective Kv1.3 blockade reduced lymphoid organ enlargement, autoantibody production, and renal pathology. In EAE models, these peptides attenuated neuroinflammation and demyelination. Their ability to modulate pathological immune responses without broad immunosuppression underscores their therapeutic promise.Conclusions Venom-derived Kv1.3-blocking peptides represent a novel and promising class of immunomodulatory agents. Their selective mechanism of action supports the development of next-generation precision immunotherapies for autoimmune diseases. Continued optimization and clinical translation may position these biologically inspired molecules as valuable additions to the therapeutic arsenal for AD management.